CONICET | Buscador de Institutos y Recursos Humanos

Background/Aims: Progesterone (P 4 ) fall provoked by spontaneous or prostaglandin F2 (PGF2 )-induced luteolysis in late pregnant rats triggers a prolactin (PRL) surge 12?24 h later. Methods: To investigate the hypothalamic mechanismmediating this response, we determined expression of tyrosine hydroxylase (TH), PRL receptors (long form, PRLR long ), estrogen- (ER ) and ER , P 4 (PR) A and B, and STAT5a, STAT5b, suppressors of cytokine signaling 1 (SOCS1), SOCS3 and CIS at mRNA (by semiquantitative and real-time RT-PCR) and protein (by Western blot only for TH, ER and PRs) levels, and dopamine and DOPAC (by high-performance liquid chromatography) contents in the mediobasal hypothalamus (MBH) 24 h after luteolysis induced by a PGF2 analogue (cloprostenol, 25 g/rat s.c. at 8 and 12 h on day 19 of pregnancy). Results: PGF2 treatment decreased circulating P 4 and estradiol and increased PRL and the estradiol/P 4 ratio. MBH DOPAC and DOPAC/dopamine ratio fell, indicating decreased dopaminergic transmission. PRLR long , PRB and ER mRNA increased. ER and PR proteins were not modified. However, TH protein and mRNA did not change. PRA, the small PR isoform, was much more abundant than PRB, the isoform considered to mediate P 4 genomic actions. STAT5a, SOCS1 and SOCS3 mRNA were also increased. Conclusion: The P 4 fall induced by PGF2 treatment induces PRL release through diminution in MBH dopaminergic transmission without change in TH expression. The increased PRLR along with elevated circulating PRL may be responsible for maintaining high TH expression through activation of short-loop feedback mechanisms, counteracting the effect of the fall in circulating P 4 . In parallel, SOCS expression contributes to limit PRL signaling.